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The peroxidatic activities of Myoglobin and Hemoglobin, their pathological consequences and possible medical interventions.

Wilson, Michael T and Reeder, Brandon J (2022) 'The peroxidatic activities of Myoglobin and Hemoglobin, their pathological consequences and possible medical interventions.' Molecular Aspects of Medicine, 84. p. 101045. ISSN 0098-2997

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Under those pathological conditions in which Myoglobin and Hemoglobin escape their cellular environments and are thus separated from cellular reductive/protective systems, the inherent peroxidase activities of these proteins can be expressed. This activity leads to the formation of the highly oxidizing oxo-ferryl species. Evidence that this happens in vivo is provided by the formation of a covalent bond between the heme group and the protein and this acts as an unambiguous biomarker for the presence of the oxo ferryl form. The peroxidatic activity also leads to the oxidation of lipids, the products of which can be powerful vasoconstrictive agents (e.g. isoprostanes, neuroprostanes). Here we review the evidence that lipid oxidation occurs following rhabdomyolysis and sub-arachnoid hemorrhage and that the products formed from arachidonic acid chains of phospholipids lead, through vasoconstriction, to kidney failure and brain vasospasm. Intervention in these pathological conditions through administration of reducing agents to remove ferryl heme is discussed. Through-protein electron transfer pathways that facilitate ferryl reduction at low reductant concentration have been identified. We conclude with consideration of the therapeutic use of Hemoglobin Based Oxygen carriers and how the toxicity of these may be reduced by engineering such electron transfer pathways into hemoglobin.

Item Type: Article
Uncontrolled Keywords: Hemoglobin; Myoglobin; Peroxidase; Blood substitute; Rhabdomyolysis; Ferryl
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Nov 2021 11:39
Last Modified: 15 Apr 2022 13:01

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